Synthesis of Ethers via Reaction of Carbanions and Monoperoxyacetals

Shiva Kumar Kyasa, Rebecca N. Meier, Ruth A. Pardini, Tristan K. Truttmann, Keith T. Kuwata, Patrick H. Dussault

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Although transfer of electrophilic alkoxyl ("RO+") from organic peroxides to organometallics offers a complement to traditional methods for etherification, application has been limited by constraints associated with peroxide reactivity and stability. We now demonstrate that readily prepared tetrahydropyranyl monoperoxyacetals react with sp3 and sp2 organolithium and organomagnesium reagents to furnish moderate to high yields of ethers. The method is successfully applied to the synthesis of alkyl, alkenyl, aryl, heteroaryl, and cyclopropyl ethers, mixed O,O-acetals, and S,S,O-orthoesters. In contrast to reactions of dialkyl and alkyl/silyl peroxides, the displacements of monoperoxyacetals provide no evidence for alkoxy radical intermediates. At the same time, the high yields observed for transfer of primary, secondary, or tertiary alkoxides, the latter involving attack on neopentyl oxygen, are inconsistent with an SN2 mechanism. Theoretical studies suggest a mechanism involving Lewis acid promoted insertion of organometallics into the O-O bond.

Original languageEnglish (US)
Pages (from-to)12100-12114
Number of pages15
JournalJournal of Organic Chemistry
Volume80
Issue number24
DOIs
StatePublished - Nov 11 2015

Fingerprint

Ethers
Peroxides
Organometallics
Lewis Acids
Acetals
Oxygen

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Kyasa, S. K., Meier, R. N., Pardini, R. A., Truttmann, T. K., Kuwata, K. T., & Dussault, P. H. (2015). Synthesis of Ethers via Reaction of Carbanions and Monoperoxyacetals. Journal of Organic Chemistry, 80(24), 12100-12114. https://doi.org/10.1021/acs.joc.5b02043

Synthesis of Ethers via Reaction of Carbanions and Monoperoxyacetals. / Kyasa, Shiva Kumar; Meier, Rebecca N.; Pardini, Ruth A.; Truttmann, Tristan K.; Kuwata, Keith T.; Dussault, Patrick H.

In: Journal of Organic Chemistry, Vol. 80, No. 24, 11.11.2015, p. 12100-12114.

Research output: Contribution to journalArticle

Kyasa, SK, Meier, RN, Pardini, RA, Truttmann, TK, Kuwata, KT & Dussault, PH 2015, 'Synthesis of Ethers via Reaction of Carbanions and Monoperoxyacetals', Journal of Organic Chemistry, vol. 80, no. 24, pp. 12100-12114. https://doi.org/10.1021/acs.joc.5b02043
Kyasa, Shiva Kumar ; Meier, Rebecca N. ; Pardini, Ruth A. ; Truttmann, Tristan K. ; Kuwata, Keith T. ; Dussault, Patrick H. / Synthesis of Ethers via Reaction of Carbanions and Monoperoxyacetals. In: Journal of Organic Chemistry. 2015 ; Vol. 80, No. 24. pp. 12100-12114.
@article{f1bd1dfa10b74125904b4e320a44993f,
title = "Synthesis of Ethers via Reaction of Carbanions and Monoperoxyacetals",
abstract = "Although transfer of electrophilic alkoxyl ({"}RO+{"}) from organic peroxides to organometallics offers a complement to traditional methods for etherification, application has been limited by constraints associated with peroxide reactivity and stability. We now demonstrate that readily prepared tetrahydropyranyl monoperoxyacetals react with sp3 and sp2 organolithium and organomagnesium reagents to furnish moderate to high yields of ethers. The method is successfully applied to the synthesis of alkyl, alkenyl, aryl, heteroaryl, and cyclopropyl ethers, mixed O,O-acetals, and S,S,O-orthoesters. In contrast to reactions of dialkyl and alkyl/silyl peroxides, the displacements of monoperoxyacetals provide no evidence for alkoxy radical intermediates. At the same time, the high yields observed for transfer of primary, secondary, or tertiary alkoxides, the latter involving attack on neopentyl oxygen, are inconsistent with an SN2 mechanism. Theoretical studies suggest a mechanism involving Lewis acid promoted insertion of organometallics into the O-O bond.",
author = "Kyasa, {Shiva Kumar} and Meier, {Rebecca N.} and Pardini, {Ruth A.} and Truttmann, {Tristan K.} and Kuwata, {Keith T.} and Dussault, {Patrick H.}",
year = "2015",
month = "11",
day = "11",
doi = "10.1021/acs.joc.5b02043",
language = "English (US)",
volume = "80",
pages = "12100--12114",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "24",

}

TY - JOUR

T1 - Synthesis of Ethers via Reaction of Carbanions and Monoperoxyacetals

AU - Kyasa, Shiva Kumar

AU - Meier, Rebecca N.

AU - Pardini, Ruth A.

AU - Truttmann, Tristan K.

AU - Kuwata, Keith T.

AU - Dussault, Patrick H.

PY - 2015/11/11

Y1 - 2015/11/11

N2 - Although transfer of electrophilic alkoxyl ("RO+") from organic peroxides to organometallics offers a complement to traditional methods for etherification, application has been limited by constraints associated with peroxide reactivity and stability. We now demonstrate that readily prepared tetrahydropyranyl monoperoxyacetals react with sp3 and sp2 organolithium and organomagnesium reagents to furnish moderate to high yields of ethers. The method is successfully applied to the synthesis of alkyl, alkenyl, aryl, heteroaryl, and cyclopropyl ethers, mixed O,O-acetals, and S,S,O-orthoesters. In contrast to reactions of dialkyl and alkyl/silyl peroxides, the displacements of monoperoxyacetals provide no evidence for alkoxy radical intermediates. At the same time, the high yields observed for transfer of primary, secondary, or tertiary alkoxides, the latter involving attack on neopentyl oxygen, are inconsistent with an SN2 mechanism. Theoretical studies suggest a mechanism involving Lewis acid promoted insertion of organometallics into the O-O bond.

AB - Although transfer of electrophilic alkoxyl ("RO+") from organic peroxides to organometallics offers a complement to traditional methods for etherification, application has been limited by constraints associated with peroxide reactivity and stability. We now demonstrate that readily prepared tetrahydropyranyl monoperoxyacetals react with sp3 and sp2 organolithium and organomagnesium reagents to furnish moderate to high yields of ethers. The method is successfully applied to the synthesis of alkyl, alkenyl, aryl, heteroaryl, and cyclopropyl ethers, mixed O,O-acetals, and S,S,O-orthoesters. In contrast to reactions of dialkyl and alkyl/silyl peroxides, the displacements of monoperoxyacetals provide no evidence for alkoxy radical intermediates. At the same time, the high yields observed for transfer of primary, secondary, or tertiary alkoxides, the latter involving attack on neopentyl oxygen, are inconsistent with an SN2 mechanism. Theoretical studies suggest a mechanism involving Lewis acid promoted insertion of organometallics into the O-O bond.

UR - http://www.scopus.com/inward/record.url?scp=84952837664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84952837664&partnerID=8YFLogxK

U2 - 10.1021/acs.joc.5b02043

DO - 10.1021/acs.joc.5b02043

M3 - Article

C2 - 26560686

AN - SCOPUS:84952837664

VL - 80

SP - 12100

EP - 12114

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 24

ER -